The presently disclosed inventive concept(s) relates to, but is not limited to, anti-CAP37 antibodies, isoforms of CAP37, methods for detecting chronic and acute inflammatory-associated diseases, and methods of treatment using the anti-CAP37 antibodies.
Cationic Antimicrobial Protein of Mr 37 kDa (CAP37) was originally isolated from granule extracts of human polymorphonuclear leukocytes (PMN) in 1984 (1). The amino acid sequence of PMN-CAP37 revealed its relation to members of the serine protease family that have a conserved catalytic active site consisting of his-57, asp-102 and ser-195 in the charge relay system (2). Of these sites, the conserved histidine and serine of the catalytic triad have been replaced with serine and glycine residues, respectively, rendering CAP37 ineffective as a serine protease (2,3). However, CAP37 has been demonstrated to have a diverse and exciting repertoire of functions. It was first analyzed regarding its bactericidal properties against Gram negative bacteria including, but not limited to, Salmonella typhimurium, Escherichia coli and Pseudomonas aeruginosa (4) and its ability to bind to and neutralize lipopolysaccharide (LPS)(5). Subsequently CAP37 was shown to be a potent chemoattractant for monocytes (6). Additionally, regarding its effects on the monocyte, CAP37 has been reported to stimulate their survival and thrombospondin secretion (7), also to enhance the LPS-stimulated release of prostaglandin E2 (8), interleukin 6 (IL-6)(9) and tumor necrosis factor-alpha (TNFα)(8-10). To add even further to its extensive range of known functions, CAP37 has been demonstrated to stimulate the reversible contraction of fibroblasts and endothelial cells (7) and to activate endothelial cell protein kinase C(PKC)(11). Recently, CAP37 released from stimulated PMN was reported to be taken up and sequestered in nearby endothelial mitochondria and has been suggested to protect against apoptosis (12).
The presence of CAP37 in the endothelium of Alzheimer's brain microvessels has been shown to be induced in rat brain endothelial cells in response to stimulation with the inflammatory molecules TNFα, interleukin 1-alpha (IL-1α) and LPS (13). There is also evidence that both Alzheimer's disease (AD) and atherosclerosis are inflammatory-associated (modulated) diseases (14, 15) in which inflammation and associated mediators can exacerbate or augment the disease.